tbuckley/cabot-search huggingface dataset:
A phase I/IIa, open-label, multicenter, non-randomized clinical trial to assess the safety and efficacy of CYNK-001 in combination with recombinant human interleukin 2 in adults with recurrent resection eligible IDH1 wild-type glioblastoma (GBM).
Authors: Daniela Annenelie Bota, Behnam Badie, Amy B. Heimberger, Nazanin Majd, Mark S. Awadalla, John Colerangle, Shawn He, Sharmila Koppisetti, William van der Touw, Robert Hariri, Andrew L Pecora
Journal: Journal of Clinical Oncology (2022)

TPS2080 Background: CYNK-001 is a CD56+CD3- enriched, off-the-shelf, allogeneic natural killer (NK) cell product expanded from placental CD34 cells. CYNK-001 exhibits in vitro cytotoxicity against patient-derived GBM cell lines and secretes cytolytic cytokines during co-culture with cancer cells. CYNK-001 administered via the intracranial (IC) route exhibited in vivo antitumor activity in a U-87MG orthotopic mouse model. Methods: A Phase I/IIa clinical trial is enrolling IDH1 wild-type GBM patients at first or second recurrence with contrast-enhancing measurable disease (per RANO criteria) who are candidate for surgical resection. Screening MRI scans for inclusion are performed within 14 days prior to Day -5 lymphodepletion with Cyclophosphamide 900mg/m 2 and fludarabine 30mg/m 2 plus mesna. Using a standard 3+3 dose escalation schema, patients will receive the first cycle of CYNK-001 intravenously (IV) at an initial dose of 2.4 x10 9 cells on Days 1, 8 and 15 after lymphodepletion. Cell supportive IL-2 at 6M IU administered SQ on Days 1, 3, 5, 8, 10, 12, and 15 within 3 hours prior to CYNK-001 IV infusion where applicable. Cycle 2 begins with surgical resection on Day 22 in which CYNK-001 is administered directly into the tumor cavity wall at an initial dose of 100 x10 6 NK cells and an Ommaya catheter placement. Subsequent CYNK-001 IC administrations via the Ommaya are on days 29 and 36 with 6M IU IL-2 SQ. DLT is evaluated for all dosing cohorts from day 1 to 7 days post last dose of cycle 2. Once a maximum tolerated dose is identified, a safety lead-in cohort with an additional 3 cycles of CYNK-001 IC will be administered prior to initiating the Phase IIa portion of the study. Endpoints: The primary endpoint is dose-limiting toxicity for the Phase I analysis and 6-month progression free survival post tumor resection for the Phase IIa component. Post-resected tumor tissue will be characterized for effector immune cell function and immune suppression with assessments directed at CYNK-001 tumor distribution using methodology developed at Celularity Inc. Approximately 66 patients are planned for this Phase I/IIa study. Approximately 66 patients are planned for this Phase I/IIa study. Clinical trial information: NCT05218408.
Saving TIME: Accuracy of a text intervention to minimize the time burden of cancer care.
Authors: Erin Mary Bange, Kerry Q. Coughlin, Timothy J Brown, Wenrui Li, Elizabeth Moriarty, Tara E. Bange, Roy Rosin, Michael Josephs, David R. Smith, Roger B. Cohen, Kelly D. Getz, Daniel Ragusano, Eesha Balar, Lynn Mara Schuchter, Mohan Balachandran, Qi Long, Lawrence N. Shulman, Carmen Guerra, Ronac Mamtani
Journal: Journal of Clinical Oncology (2022)

6527 Background: Patients with cancer spend substantial time receiving cancer care. There is a need for innovative strategies to decrease the time burden of cancer therapy. The current care model consists largely of in-person visits to assess treatment toxicity. Most patients treated with immunotherapy, however, do not experience substantial toxicity. We designed and evaluated a text-based instrument to identify patients without symptoms of immunotherapy toxicity. This instrument has the potential to be combined with lab assessment to identify individuals who can safely proceed directly to treatment, lessening the need for in-person office visits. Methods: This cross-sectional study evaluated the performance characteristics of a text-based instrument to identify patient-reported immunotherapy toxicity, against the gold standard in-person provider assessment documented in the electronic medical record (EMR). Those eligible for inclusion spoke English, were receiving single agent immune checkpoint blockade for a solid tumor, and had access to a mobile device with text messaging capabilities. The instrument contained 16 questions adapted from the NCI Pro-CTCAE and was administered via text-message 96 hours prior to the patient’s scheduled infusion visit. Patient perspectives were quantified via a 13-item questionnaire. Results: Between October 1 and November 25, 2021, 50 patients enrolled in the study, and 45 patients completed the instrument (90% response). The median age was 68 (IQR 60-72), 31 (62%) were male, and 44 (88%) were white. Most patients received either pembrolizumab (n=27, 54%) or nivolumab (n=17, 34%) in the palliative setting (n=37, 74%) for genitourinary (n=15, 30%), lung (n=13, 26%), or skin (n=11, 22%) cancer. Patients who completed the instrument were younger (median age 67 vs 76) than those who did not complete the instrument. The prevalence of immune related toxicity documented in the EMR was 57.8%. The sensitivity and negative predictive value of the instrument was 100% (95% CI 0.87-1.00) and 100% (95% CI 0.664-1.00), respectively; other accuracy parameters are presented in the Table. The patient user questionnaire revealed that visual impairment, lack of access to a smart phone, and lack of recognition of the instrument were barriers to completion. Conclusions: A text-based platform is both feasible and effective at identifying patients who are not experiencing symptoms of immune toxicity, and when combined with lab assessment, can eliminate office visits for up to 47% of patients. A prospective clinical trial to assess this is underway (NCT05134636). [Table: see text]
Overcoming barriers in academic-industry partnerships to improve predictive modeling in immuno-oncology.
Authors: Kathleen F. Mittendorf, Christine Micheel, Michele LeNoue-Newton, Protiva Rahman, Daniel Fabbri, Jan Wolber, Travis John Osterman, Mohamed Fouda, Ben Ho Park
Journal: Journal of Clinical Oncology (2022)

e13581 Background: In the past decade, immunotherapies have revolutionized oncology practice by prolonging patient survival in previously rapidly fatal cancers. However, severe immune toxicities present a challenge, affecting ̃20% and up to 50% of patients on immune monotherapies and combination immunotherapies, respectively. Oncologists must balance toxicity risk with potential efficacy, and pharmaceutical companies have a vested interest in selecting patients with the highest benefit–risk ratio during trial enrollment. Predictive toxicity–efficacy modeling has the potential to guide trial subject selection and clinical care, yet there remains a need for predictive models that can be practically implemented in these settings. Methods: A common academic–industry contract data–transfer framework—wherein academic medical institutions and industry counterparts act in isolation—creates barriers to development of high-quality algorithms with practical applications. In this framework, 1) academic medical institutions provide patient data as a “data dump;” these data are static and cannot be refined—reducing opportunities for quality control; 2) predictive model outcomes may include artifacts that are not identified; 3) manual curation of patient data is required to accurately replicate the model in real-world settings; and 4) lack of clinician participation reduces the potential clinical applications of models and reciprocal benefit to the academic institution. We outline a more contemporary, engaged approach to unite strengths of both partners to achieve a common goal. Results: In 2019, Vanderbilt University Medical Center and GE Healthcare partnered with the goal of enabling safer and more precise immunotherapy use. As part of this work, we formulated a recipe for academic–industry partnerships that offers unique advantages over a static contract framework. In our iterative, interactive approach, 1) clinical and curation experts meet with industry modelers to dynamically refine deidentified data sets by resolving discrepancies in data from different sources (e.g., manually curated vs. structured data); 2) clinical experts iteratively review outputs of predictive models to identify potential artifacts and refine final models; 3) expert curators iterate with in-house machine-learning experts to create algorithms to automate curation of natural language elements from the identified EHR data; and 4) clinical and industry stakeholders participate in regular meetings with modelers to ensure clinical and trial utility of the modeling approach. Conclusions: Compared to data transfer-only relationships, this partnership framework offers an opportunity to develop more informed, higher quality immunotherapy models with clinical and industry applications.
Impact of COVID-19 on risk of venous thromboembolism (VTE) in cancer patients: A single institution analysis.
Authors: Aneesha Ananthula, Katharine Thomas, Dat Tran, Anh Nguyen, Katie Lauren McLemore McQueen Amaker, Brandon T Thrash, William Gibson, Monique Germain, Shyam Mani, Andrew G Chapple, Suki Subbiah
Journal: Journal of Clinical Oncology (2022)

e18732 Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status; 2) assess the relative risk of VTE due to COVID-19 in cancer patients; 3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) [RR 3.45, 95% CI 1.85-6.67]. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.
Non-variceal upper gastrointestinal bleeding in patients with acute leukemia.
Authors: Mahmoud Mansour, Adham E. Obeidat, Yomna Abu-Farsakh, Ratib Mahfouz, Mohammad Darweesh, Ghulam Ghous, Veysel Tahan
Journal: Journal of Clinical Oncology (2022)

e19041 Background: Patients with acute leukemia are prone to various hemorrhages, most frequently due to thrombocytopenia from disease activity or chemotherapy. However, there is minimal literature evaluating non-variceal upper gastrointestinal bleeding (NVUGIB) in leukemia patients. This study evaluates the outcomes of NVUGIB in hospitalized acute leukemia patients. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between Jan 1st, 2016, to Dec 31st, 2019. Using International Classification of Diseases 10th revision codes, we identified adults with a discharge diagnosis of NVUGIB and a concomitant acute leukemia diagnosis, acute myelogenous leukemia and acute lymphoblastic leukemia. The control group included non-leukemia patients with NVUGIB. Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS), hospital charges, and effect of early esophagogastroduodenoscopy (EGD) within the first 24 hours of admission. Multivariate logistic regression was used to adjust for comorbidities and demographic variables. Results: A total of 1,208,885 discharges were identified with NVUGIB. Of those, 1019 had acute leukemia. Leukemia patients had higher mortality than the general population (12.5% vs. 3%, respectively; P &lt;0.01). After adjusting for comorbidities and demographic variables, acute leukemia patients had significantly higher mortality (adjusted odds ratio [AOR] 3.75, 95%CI 2.37-5.94 P &lt;0.01). Mean length of stay and hospital charges increased by 6.87 days (95%CI 3.99-9.75, P &lt; 0.01) and 128,437$ (95%CI 68,633$-188,240$, P &lt; 0.01), respectively, in the acute leukemia group. Additionally, acute leukemia patients who had an early EGD had significantly less mortality, length of stay, and hospital charges compared to delayed EGD as shown in the attached table. Conclusions: Acute leukemia patients admitted with NVUGIB have significantly higher in-hospital mortality and health care burden. Early EGD in these patients is associated with lower in-hospital mortality, shorter length of stay, and lower total hospital costs. However, given the retrospective nature of this study, we cannot determine that early EGD is a causal factor for the improved outcomes. Future prospective studies will be required in acute leukemia patients admitted with NVUGIB to further evaluate these findings.[Table: see text]
Modified CARG score using data from the electronic health record to predict chemotherapy toxicity in older adults.
Authors: Jasmine L Martin, Kathie Wu, Mudit Gupta, Alicia M Johns, Christian S. Adonizio
Journal: Journal of Clinical Oncology (2022)

12038 Background: Older adults starting chemotherapy are at greater risk of toxicity compared with younger patients. Additional tools are needed to aid in management decisions for this population. The Cancer and Aging Research Group (CARG) chemotherapy toxicity calculator is one such tool, which stratifies older adults into high, intermediate, or low risk for chemotherapy toxicity (Hurria, A., Mohile, S., Tew, W. P., &amp; et al. (2016). Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. Journal of Clinical Oncology, 34(20), 2366–2371. https://doi.org/10.1200/jco.2015.65.4327). This tool relies on a face-to-face encounter to ask questions, e.g. “How is your hearing?” or “Can you take your own medicines?” in addition to lab values such as hemoglobin and creatinine clearance. We modified the CARG chemo toxicity calculator to include data points which could be pulled from the electronic health record (EHR) without the need for a face-to-face encounter to assess for an association with emergency department (ED) visits and hospital admissions. Methods: Retrospective data analysis was conducted using the EHR of patients over age 65 diagnosed with a solid tumor from 1/1/2019 to 12/31/2020 who started chemotherapy. A modified CARG score was calculated using age, cancer type, number of drugs, hemoglobin, creatinine clearance, and falls within the past 6 months. The remaining items needed to calculate the complete CARG score were excluded since they were not accessible in the EHR. We assessed ED visits leading to admission, ED visits leading to discharge, direct admissions, and the total of all 3 visit types for all patients. Results: A modified CARG score was calculated for 763 patients. Multiple models were evaluated and negative binomial distribution was found to be the best fitted for our data. For every one unit increase in our calculated score the number of ED visits which lead to hospital admission increased by 6% (p-value = 0.0156). Additionally, there was a 5% increase in combined ED visits, ED visits leading to admission, and direct admissions for every one unit increase in risk score (p-value = 0.0063). ED visits that did not lead to admission were found not to have an association with the risk score (p-value= 0.1263). (Table) Conclusions: A modified CARG score using data obtained from patients’ EHR had a statistically significant association with increased ER visits that resulted in hospital admission and with the total of ED visits leading to admission, ED visits leading to discharge, direct admissions. Using these outcomes as a surrogate for toxicity, we deduce that a simple tool could be used to predict chemotherapy toxicity in older adults. [Table: see text]
Davoceticept (ALPN-202), a PD-L1-dependent CD28 costimulator and dual checkpoint inhibitor, in combination with pembrolizumab in patients with advanced malignancies (NEON-2).
Authors: Amita Patnaik, Nehal J. Lakhani, Meredith McKean, Justin F. Gainor, Cathy Vo Buu, Stacey R. Dillon, Hany Zayed, Michael Jon Chisamore, James Michael Pluda, Stanford L. Peng
Journal: Journal of Clinical Oncology (2022)

TPS2683 Background: Despite successes with checkpoint inhibition (CPI) in a wide range of tumors, most demonstrate primary or acquired resistance, warranting better therapeutic strategies. PD-1 is now recognized to effect much of its benefit by disinhibiting CD28 signaling – a mechanism expected to require intra-tumoral engagement of CD28 by its ligands CD80/CD86. Davoceticept (ALPN-202), a variant CD80 vIgD-Fc fusion protein, was engineered to provide tumor localizing PD-L1-dependent CD28 agonism, while inhibiting PD-L1 and CTLA-4. Davoceticept has demonstrated superiority to CPI-only therapies in both in vitro and in vivo tumor models, while also demonstrating additional benefit in combination with targeted PD-1 axis blockade (Lewis et al. (2019) J Immunother Cancer 7(S1): P467). The benefit appeared at least additive in models of poorly immunogenic tumors, suggesting the possibility of meaningful clinical benefit where CPI therapeutic efficacy is limited, such as noninflamed tumors. Single agent safety and tolerability of davoceticept has been demonstrated along with pharmacodynamic evidence of CD28 engagement with immune checkpoint inhibition (Moser et al. (2021) J Clin Oncol 39(s15): 2547). Methods: NEON-2 is an open-label dose escalation and expansion study of davoceticept combined with pembrolizumab in adults with advanced solid tumors or lymphoma that was initiated in June 2021 (NCT04920383). Eligibility includes tumors where single agent PD-(L)1 antagonists are SOC, are refractory or resistant to standard therapies (including approved CPIs), or have no standard or curative therapy. The study employs a standard 3+3 dose escalation design with two schedules, Q1W and Q3W of davoceticept. Pembrolizumab is given per label at 400 mg IV Q6W. Objectives include evaluation of safety and tolerability, identification of the recommended phase 2 dose(s) (RP2D), PK, PD, exploratory predictive biomarker analysis (i.e., PD-L1, CD28, CD80 and CD86 expression, as well as immunophenotyping of immune cell populations on treatment) and preliminary anticancer activity of davoceticept in combination with pembrolizumab. Disease assessments are evaluated by RECIST v1.1 for solid tumors or by Lugano Classification for lymphoma. Efficacy endpoints include ORR, duration of response and disease control rate. Once the RP2D combination is identified, tumor-specific expansion cohorts of ̃ 30- 35 patients will be performed, including histologies that have not been demonstrated to be CPI responsive, as well as those where CPIs are approved SOC. The 0.1 mg/kg cohorts have been completed without DLT. Enrollment to the 0.3 mg/kg cohorts began in September 2021. Clinical trial information: NCT04920383.
Effect of deep neuromuscular block on surgical pleth index-guided remifentanil administration in <i>the elderly</i> undergoing laparoscopic gastrectomy for gastric cancer.
Authors: Ji Eun Kim
Journal: Journal of Clinical Oncology (2022)

e16048 Background: Deep neuromuscular block (NMB) has been increasingly utilized in laparoscopic oncologic surgery, but its role in reducing intraoperative opioid requirement has yet to be investigated. Opioid in cancer patients is related with immunosuppression. Surgical pleth index (SPI) quantifies nociception. We investigated the effects of deep NMB on remifentanil requirements in the elderly patients undergoing laparoscopic gastrectomy under SPI-guided anesthesia. Methods: In this randomized controlled trial, the elderly patients aged 60–85 years who underwent laparoscopic gastrectomy for gastric cancer were included. Arrythmia, peripheral vascular disease and chronic opioid user were excluded. The patients (n = 60) were randomly allocated into deep (n = 30) or moderate (n = 30) NMB groups between December 2019 and December 2020. The moderate NMB group was maintained as Train-of-four count 1-2 during surgery and revered using neostigmine 50 ug/kg after the end of surgery. The deep NMB group was maintained as post-tetanic count 1-2 and reversed with using sugammadex 4 mg/k. The remifentanil dose was assessed during intubation, from skin incision until CO 2 insertion, and pneumoperitoneum. Results: Demographic, hemodynamic and operational data were similar between two groups, except rocuronium dose. The remifentanil doses administered for tracheal intubation and during time from skin incision until CO 2 insertion were similar (P = 0.412 and P = 0.649). In addition, total dose of remifentanil administered during pneumoperitoneum was not significantly different between two groups (P = 0.315), which remains non-significant when adjusted by weight, duration or both (P = 0.603, P = 0.146, and P = 0.389). Consequently, total dose of remifentanil administered during anesthesia was not different (P = 0.247). In post-anesthesia care unit, the pain score and the number of patients receiving analgesics were not different (P = 0.064 and P = 0.773). However, the duration of post-anesthesia care unit stay was significantly lower in the deep NMB group compared with in the moderate NMB group (P = 0.011). Conclusions: Deep NMB did not reduce the remifentanil requirement compared with moderate NMB in the elderly patients undergoing laparoscopic gastrectomy under SPI-guided anesthesia. Clinical trial information: NCT04205097.